title: Increased risk of pneumonia and bronchiolitis after bacterial colonization of the airways as neonates.
abstract: BACKGROUND
  The frequency of pneumonia and bronchiolitis exhibits considerable variation in otherwise healthy children, and suspected risk factors explain only a minor proportion of the variation. We hypothesized that alterations in the airway microbiome in early life may be associated with susceptibility to pneumonia and bronchiolitis in young children.
  
  
  OBJECTIVE
  To investigate the relation between neonatal airway colonization and pneumonia and bronchiolitis during the first 3 years of life.
  
  
  METHODS
  Participants comprised children of the Copenhagen Prospective Studies on Asthma in Childhood2000 (COPSAC2000) cohort, a prospective birth cohort study of 411 children born to mothers with asthma. Aspirates from the hypopharynx at age 4 weeks were cultured for Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus. Clinical information on pneumonia and bronchiolitis within the first 3 years of life was prospectively collected by the research physicians at the center. Analyses were adjusted for covariates associated with pneumonia and bronchiolitis and bacterial airway colonization.
  
  
  RESULTS
  Hypopharyngeal aspirates and full clinical follow-up until 3 years of age were available for 265 children. Of these, 56 (21%) neonates were colonized with S. pneumoniae, H. influenzae, and/or M. catarrhalis at 4 weeks of age. Colonization with at least one of these microorganisms (but not S. aureus) was significantly associated with increased incidence of pneumonia and bronchiolitis (adjusted incidence rate ratio, 1.79 [1.29-2.48]; P < 0.005) independently of concurrent or later asthma.
  
  
  CONCLUSIONS
  Neonatal airway colonization with S. pneumoniae, H. influenzae, or M. catarrhalis is associated with increased risk of pneumonia and bronchiolitis in early life independently of asthma. This suggests a role of pathogenic bacterial colonization of the airways in neonates for subsequent susceptibly to pneumonia and bronchiolitis.
authors.affiliation: 1 Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen and Copenhagen University Hospital, Gentofte, Copenhagen, Denmark.
authors.forename: Nadja H
authors.initials: NH
authors.lastname: Vissing
authors.forename: Bo L K
authors.initials: BL
authors.lastname: Chawes
authors.forename: Hans
authors.initials: H
authors.lastname: Bisgaard
mesh_terms: D001249:Asthma / Q000175:diagnosis / Q000453:epidemiology / Q000382:microbiology; D001988:Bronchiolitis / Q000175:diagnosis / Q000453:epidemiology / Q000382:microbiology*; D002675:Child, Preschool; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006193:Haemophilus influenzae / Q000302:isolation & purification; D006801:Humans; D007013:Hypopharynx / Q000382:microbiology*; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D008297:Male; D064307:Microbiota; D001936:Moraxella catarrhalis / Q000302:isolation & purification; D011014:Pneumonia / Q000175:diagnosis / Q000453:epidemiology / Q000382:microbiology*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D013211:Staphylococcus aureus / Q000302:isolation & purification; D013296:Streptococcus pneumoniae / Q000302:isolation & purification